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Neurologie up2date 2018; 1(01): 83-103
DOI: 10.1055/a-0657-7631
Myopathien und Neuropathien
Georg Thieme Verlag KG Stuttgart · New York

Diagnostik und Therapie der Muskeldystrophien

Rudolf Korinthenberg
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Publication History

Publication Date:
04 October 2018 (online)

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Die Muskeldystrophien stellen eine sehr variable Gruppe genetischer Muskelerkrankungen dar. Die häufigste Unterform Duchenne-Muskeldystrophie beginnt bereits im frühen Kindesalter und interessiert zunächst vor allem Kinderärzte und Kinderneurologen. Das heute jahrzehntelange Überleben führt diese Patienten aber zunehmend in die Betreuung der Erwachsenenmedizin. Seltener sind die Typen mit Manifestation im Jugend- und Erwachsenenalter, die primär vom Neurologen zu erkennen und zu betreuen sind.
Kernaussagen

  • Die Diagnose einer Muskeldystrophie (MD) beruht weiterhin zunächst auf klinischem Bild, Alter, Geschlecht und Familienanamnese. Serum-Kreatinkinase, EMG und Bildgebung des Muskels können hilfreich sein.

  • Die Muskeldystrophien Duchenne und Becker sind beim männlichen Geschlecht in allen Altersstufen die bei Weitem häufigsten Typen. Deshalb sollte bei passendem Phänotyp eine MLPA (Multiplex Ligation-dependent Probe Amplification) oder Array-CGH (comparative genomic Hybridization) des Dystrophin-Gens veranlasst werden.

  • Bei negativem Befund und abhängig vom Phänotyp ist die genetische Diagnostik anschließend zu erweitern und ggf. eine Muskelbiopsie indiziert.

  • Patienten mit MD müssen in Abhängigkeit von Schwere und Verlauf der Erkrankung konsequent mit Physiotherapie, Ergotherapie sowie orthopädisch behandelt und mit Hilfsmitteln versorgt werden. Entsprechende Standards sind publiziert worden.

  • Die genetische Diagnose führt zu dem Wissen, welche Patienten durch eine zum Teil rasche respiratorische oder kardiale Verschlechterung bedroht sind. Diese benötigen ein prospektives Monitoring und eine zeitgerechte Therapie.

  • Zahlreiche laufende Therapiestudien lassen für die Zukunft deutliche Fortschritte in der Behandlung der MD erhoffen. Die bislang erzielten Effekte sind aber noch verhältnismäßig gering, betreffen nur einzelne Patientengruppen oder sind im Fall der Kortikosteroide mit ernsten Nebenwirkungen behaftet.

 

  • Literatur

  • 1 Koenig M, Hoffmann EP, Bertelson CJ. et al. Complete cloning of the Duchenne muscular dystrophy (DMD) cDNA and preliminary genomic organization of the DMD gene in normal and affected individuals. Cell 1987; 48: 351-357
    CrossrefPubMedGoogle Scholar
  • 2 Domingos J, Sarkozy A, Scoto M. et al. Dystrophinopathies and limb-girdle muscular dystrophies. Neuropediatrics 2017; 48: 262-272
    Article in Thieme ConnectPubMedGoogle Scholar
  • 3 Kirschner J, Bönnemann CG. The congenital and limb-girdle muscular dystrophies. Sharpening the focus, blurring the boundaries. Arch Neurol 2004; 61: 189-199
    CrossrefPubMedGoogle Scholar
  • 4 Vissing J. Limb girdle muscular dystrophies: classification, clinical spectrum and emerging therapies. Curr Opin Neurol 2016; 29: 635-641
    CrossrefPubMedGoogle Scholar
  • 5 Magri F, Nigro V, Angelini C. et al. The Italian limb girdle muscular dystrophy registry: Relative frequency, clinical features, and differential diagnosis. Muscle Nerve 2017; 55: 55-68
    CrossrefPubMedGoogle Scholar
  • 6 van Putten M, Aartsma-Rus A, Grounds MD. et al. Update on standard operating procedures in preclinical research for DMD and SMA. Report of TREAT-NMD Alliance Workshop, Schiphol Airport, 26 April 2015, The Netherlands. J Neuromuscul Dis 2018; 5: 29-34
    PubMedGoogle Scholar
  • 7 Reinig AM, Mirzaei S, Berlau DJ. Advances in the treatment of Duchenne muscular dystrophy: new and emerging pharmacotherapies. Pharmacotherapy 2017; 37: 492-499
    CrossrefPubMedGoogle Scholar
  • 8 Schuntermann MF. The implementation of the International Classification of Functioning, Disability and Health in Germany: experiences and problems. Int J Rehabil Res 2005; 28: 93-102
    CrossrefPubMedGoogle Scholar
  • 9 Bushby K, Finkel R, Birnkrant DJ. et al. Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, and pharmacological and psychosocial management. Lancet Neurol 2010; 9: 77-93
    CrossrefPubMedGoogle Scholar
  • 10 Bushby K, Finkel R, Birnkrant DJ. et al. Diagnosis and management of Duchenne muscular dystrophy, part 2: implementation of multidisciplinary care. Lancet Neurol 2010; 9: 177-189
    CrossrefPubMedGoogle Scholar
  • 11 Birnkrant DJ, Bushby K, Bann CM. et al. Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, and neuromuscular, rehabilitation, endocrine, and gastrointestinal and nutritional management. Lancet Neurol 2018; 17: 251-267
    CrossrefPubMedGoogle Scholar
  • 12 Birnkrant DJ, Bushby K, Bann CM. et al. Diagnosis and management of Duchenne muscular dystrophy, part 2: respiratory, cardiac, bone health, and orthopaedic management. Lancet Neurol 2018; 17: 347-361
    CrossrefPubMedGoogle Scholar
  • 13 Birnkrant DJ, Bushby K, Bann CM. et al. Diagnosis and management of Duchenne muscular dystrophy, part 3: primary care, emergency management, psychosocial care, and transitions of care across the lifespan. Lancet Neurol 2018; 17: 445-455
    CrossrefPubMedGoogle Scholar
  • 14 Jeppesen J, Green A, Steffensen BF. et al. The Duchenne muscular dystrophy population in Denmark, 1977-2001: prevalence, incidence and survival in relation to the introduction of ventilator use. Neuromuscul Disord 2003; 13: 804-812
    CrossrefPubMedGoogle Scholar
  • 15 Narayanaswami P, Weiss M, Selcen D. et al. Evidence-based guideline summary: diagnosis and treatment of limb-girdle and distal dystrophies: report of the guideline development subcommittee of the American Academy of Neurology and the practice issues review panel of the American Association of Neuromuscular & Electrodiagnostic Medicine. Neurology 2014; 83: 1453-1463
    CrossrefPubMedGoogle Scholar
  • 16 Silvestri NJ, Ismail H, Zimetbaum P. et al. Cardiac involvement in the muscular dystrophies. Muscle Nerve 2018; 57: 707-715
    CrossrefPubMedGoogle Scholar
  • 17 Wattjes MP, Kley RA, Fischer D. Neuromuscular imaging in inherited muscle diseases. Eur Radiol 2010; 20: 2447-2460
    CrossrefPubMedGoogle Scholar
  • 18 Ten Dam L, van der Kooi AJ, Verhamme C. et al. Muscle imaging in inherited and acquired muscle diseases. Eur J Neurol 2016; 23: 688-703
    CrossrefPubMedGoogle Scholar
  • 19 Mohassel P, Mammen AL. Anti-HMGCR-Myopathy. J Neuromuscul Dis 2018; 5: 11-20
    CrossrefPubMedGoogle Scholar
  • 20 Wang CH, Bonnemann CG, Rutkowski A. et al. Consensus statement on standard of care for congenital muscular dystrophies. J Child Neurol 2010; 25: 1559-1581
    CrossrefPubMedGoogle Scholar
  • 21 Wang CH, Dowling JJ, North K. et al. Consensus statement on standard of care for congenital myopathies. J Child Neurol 2012; 27: 363-382
    CrossrefPubMedGoogle Scholar
  • 22 Wang CH, Finkel RS, Bertini ES. et al. Consensus statement for standard of care in spinal muscular atrophy. J Child Neurol 2007; 22: 1027-1049
    CrossrefPubMedGoogle Scholar
  • 23 Finkel RS, Mercuri E, Meyer OH. et al. Diagnosis and management of spinal muscular atrophy: Part 2: Pulmonary and acute care; medications, supplements and immunizations; other organ systems; and ethics. Neuromuscular Disord 2018; 28: 197-207
    CrossrefPubMedGoogle Scholar
  • 24 Mercuri E, Finkel RS, Muntoni F. et al. Diagnosis and management of spinal muscular atrophy: Part 1: Recommendations for diagnosis, rehabilitation, orthopedic and nutritional care. Neuromuscular Disord 2018; 28: 103-115
    CrossrefPubMedGoogle Scholar
  • 25 Matthews E, Brassington R, Kuntzer T. et al. Corticosteroids for the treatment of Duchenne muscular dystrophy. Cochrane Database Syst Rev 2016; (5): CD003725. Cochrane Database Syst Rev 2016; (05) CD003725
    PubMedGoogle Scholar
  • 26 Sveen ML, Andersen SP, Ingelsrud LH. et al. Resistance training in patients with limb-girdle and Becker muscular dystrophies. Muscle Nerve 2013; 47: 163-169
    CrossrefPubMedGoogle Scholar
  • 27 Voet N, Bleijenberg G, Hendriks J. et al. Both aerobic exercise and cognitive-behavioral therapy reduce chronic fatigue in FSHD: an RCT. Neurology 2014; 83: 1914-1922
    CrossrefPubMedGoogle Scholar
  • 28 Wright NC, Kilmer DD, McCrory MA. et al. Aerobic walking in slowly progressive neuromuscular disease: effect of a 12-week program. Arch Phys Med Rehabil 1996; 77: 64-69
    CrossrefPubMedGoogle Scholar
  • 29 Cheuk DK, Wong V, Wraige E. et al. Surgery for scoliosis in Duchenne muscular dystrophy. Cochrane Database Syst Rev 2015; (10) CD005375
    PubMedGoogle Scholar
  • 30 Archer JE, Gardner AC, Roper HP. et al. Duchenne muscular dystrophy: the management of scoliosis. J Spine Surg 2016; 2: 185-194
    CrossrefPubMedGoogle Scholar
  • 31 LoMauro A, DʼAngelo MG, Aliverti A. Assessment and management of respiratory function in patients with Duchenne muscular dystrophy: current and emerging options. Ther Clin Risk Manag 2015; 11: 1475-1488
    PubMedGoogle Scholar
  • 32 Papa AA, DʼAmbrosio P, Petillo R. et al. Heart transplantation in patients with dystrophinopathic cardiomyopathy: Review of the literature and personal series. Intractable Rare Dis Res 2017; 6: 95-101
    CrossrefPubMedGoogle Scholar
  • 33 Bach JR, Campagnolo DI, Hoeman S. Life satisfaction of individuals with Duchenne muscular dystrophy using long-term mechanical ventilatory support. Am J Phys Med Rehabil 1991; 70: 129-135
    CrossrefPubMedGoogle Scholar
  • 34 Vry J, Gramsch K, Rodger S. et al. European Cross-Sectional Survey of Current Care Practices for Duchenne Muscular Dystrophy Reveals Regional and Age-Dependent Differences. J Neuromuscular Dis 2016; 3: 517-527
    Google Scholar
  • 35 Robinson-Hamm JN, Gersbach CA. Gene therapies that restore dystrophin expression for the treatment of Duchenne muscular dystrophy. Hum Genet 2016; 135: 1029-1040
    CrossrefPubMedGoogle Scholar
  • 36 Goemans NM, Tulinius M, van den Akker JT. et al. Systemic administration of PRO051 in Duchenneʼs muscular dystrophy. N Engl J Med 2011; 364: 1513-1522
    CrossrefPubMedGoogle Scholar
  • 37 Cirak S, Arechavala-Gomeza V, Guglieri M. et al. Exon skipping and dystrophin restoration in patients with Duchenne muscular dystrophy after systemic phosphorodiamidate morpholino oligomer treatment: an open-label, phase 2, dose-escalation study. Lancet 2011; 378: 595-605
    CrossrefPubMedGoogle Scholar
  • 38 Voit T, Topaloglu H, Straub V. et al. Safety and efficacy of drisapersen for the treatment of Duchenne muscular dystrophy (DEMAND II): an exploratory, randomised, placebo-controlled phase 2 study. Lancet Neurol 2014; 13: 987-996
    CrossrefPubMedGoogle Scholar
  • 39 Goemans N, Mercuri E, Belousova E. et al. A randomized placebo-controlled phase 3 trial of an antisense oligonucleotide, drisapersen, in Duchenne muscular dystrophy. Neuromuscul Disord 2018; 28: 4-15
    CrossrefPubMedGoogle Scholar
  • 40 Mendell JR, Rodino-Klapac LR, Sahenk Z. et al. Eteplirsen for the Treatment of Duchenne Muscular Dystrophy. Ann Neurol 2013; 74: 637-647
    CrossrefPubMedGoogle Scholar
  • 41 Randeree L, Eslick GD. Eteplirsen for paediatric patients with Duchenne muscular dystrophy: A pooled-analysis. J Clin Neurosci 2018; 49: 1-6
    CrossrefPubMedGoogle Scholar
  • 42 Bushby K, Finkel R, Wong B. et al. Ataluren treatment of patients with nonsense mutation dystrophinopathy. Muscle Nerve 2014; 50: 477-487
    CrossrefPubMedGoogle Scholar
  • 43 McDonald CM, Campbell C. Torricell RE,et al. Ataluren in patients with nonsense mutation Duchenne muscular dystrophy (ACT DMD): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 2017; 390: 1489-1498
    CrossrefPubMedGoogle Scholar
  • 44 Buyse GM, Voit T, Schara U. et al. Efficacy of idebenone on respiratory function in patients with Duchenne muscular dystrophy not using glucocorticoids (DELOS): a double-blind randomised placebo-controlled phase 3 trial. Lancet 2015; 385: 1748-1757
    CrossrefPubMedGoogle Scholar